Efficacy, Safety, and Tolerability Study of Pirfenidone in Combination With Sildenafil in Participants With Advanced Idiopathic Pulmonary Fibrosis (IPF) and Intermediate or High Probability of Group 3 Pulmonary Hypertension

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This Phase IIb, randomized, placebo-controlled, multicenter, international study will evaluate the efficacy, safety, and tolerability of sildenafil or placebo added to pirfenidone (Esbriet) treatment in participants with advanced IPF and intermediate or high probability of Group 3 pulmonary hypertension (PH) who are on a stable dose of pirfenidone with demonstrated tolerability. Participants will be randomized to receive 1 year of treatment with either oral sildenafil or matching placebo while continuing to take pirfenidone.

A Phase IIb, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy, Safety, and Tolerability of Sildenafil Added to Pirfenidone in Patients With Advanced Idiopathic Pulmonary Fibrosis and Intermediate or High Probability of Group 3 Pulmonary Hypertension

Percentage of Participants With Disease Progression, as Determined by Relevant Decline in 6 Minute Walk Distance (6MWD) of At Least (>=) 15 Percent (%) From Baseline, Respiratory-Related Non-Elective Hospitalization, or Death From Any Cause [ Time Frame: Baseline up to Week 52 ]

Secondary Outcome Measures :

Progression-Free Survival (PFS), Defined as Time to Decline in 6MWD of >=15% From Baseline, Respiratory-Related Non-Elective Hospitalization, or Death From Any Cause [ Time Frame: Baseline up to Week 52 ]

Percentage of Participants With Decline From Baseline in 6MWD of >= 15% [ Time Frame: Baseline up to Week 52 ]

Time to Respiratory-Related Non-Elective Hospitalization [ Time Frame: Baseline up to Week 52 ]

Time to All-Cause Non-Elective Hospitalization [ Time Frame: Baseline up to Week 52 ]

Time to Death From Any Cause [ Time Frame: Baseline up to Week 52 ]

Time to Respiratory-Related Death [ Time Frame: Baseline up to Week 52 ]

Percentage of Participants With Lung Transplantation [ Time Frame: Baseline up to Week 52 ]

Change From Baseline to Weeks 12, 26, 39, and 52 in Dyspnea, as Assessed by the University of California San Diego Shortness of Breath Questionnaire (UCSD SOBQ) [ Time Frame: Baseline, Weeks 12, 26, 39, and 52 ]

Change From Baseline to Weeks 12, 26, 39, and 52 in Health-Related Quality of Life (HRQoL), as Assessed by the Saint George's Respiratory Questionnaire (SGRQ) [ Time Frame: Baseline, Weeks 12, 26, 39, and 52 ]

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Layout table for eligibility information

Ages Eligible for Study:

40 Years to 80 Years (Adult, Older Adult)

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria:

Diagnosis of IPF for at least 3 months prior to Screening

Confirmation of IPF diagnosis by the investigator in accordance with the 2011 international consensus guidelines at screening

Advanced IPF (defined as a measurable carbon monoxide diffusing capacity [DLCO] less than or equal to (<=)40% of predicted value at Screening) and intermediate or high probability of group 3 pulmonary hypertension (PH)

Participants receiving pirfenidone for at least 12 weeks, at a dose in the range of 1602 to 2403 mg/day for at least 4 weeks prior to Screening and must not have experienced either a new or ongoing adverse event of National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) (version 4.03) Grade 2 or higher and considered by the investigator to be related to pirfenidone, or an interruption of pirfenidone treatment of greater than (>)7 days for any reason

WHO Functional Class II or III at Screening

6MWD of 100 to 450 meters at screening

Women of childbearing potential and for men who are not surgically sterile agreement to remain abstinent or use of contraceptive measures

Exclusion Criteria:

History of any of the following types of PH: Group 1 (PAH); Group 1 (pulmonary veno-occlusive disease and/or pulmonary capillary hemangiomatosis); Group 2 (left-heart disease); Group 3 (due to conditions other than interstitial lung disease, including chronic obstructive pulmonary disease [COPD], sleep-disordered breathing, alveolar hypoventilation, high altitude, or developmental abnormalities); Group 4 (chronic thromboembolic pulmonary hypertension); Group 5 (other disorders)

History of clinically significant cardiac disease

History of coexistent and clinically significant COPD, bronchiectasis, asthma, inadequately treated sleep-disordered breathing, or any clinically significant pulmonary diseases or disorders other than IPF or PH secondary to IPF

History of use of drugs and toxins known to cause PAH, including aminorex, fenfluramine, dexenfluramine, and amphetamines